Biosensors Encoded Fiber-Optic Microsphere Arrays for Probing Protein–Carbohydrate Interactions** EddieW.Adams,JörnUeberfeld,DanielM.Ratner, BarryR.O'Keefe,DavidR.Walt,*and PeterH.Seeberger* Carbohydrate-binding proteins and their glycoconjugate ligands play significant roles in a number of critical biological processes. Immune response, viral membrane fusion, glyco- protein homeostasis, and signaling all involve carbohydrate- binding protein mediation at key steps. [1] A more detailed understanding of the exact nature of carbohydrate–protein interactions is expected to render them attractive therapeutic targets. To facilitate these biochemical investigations, glyco- biologists require tools that will enable the simultaneous identification of carbohydrate-binding proteins and the oligosaccharide structures they bind. Carbohydrate microarrays were introduced as a promis- ing tool to aid in the discovery of oligosaccharide moieties necessary for carbohydrate-binding protein recognition. [2] Microarrays require small quantities of material, enable simultaneous screening of a defined set of structures against a host of potential binding partners, and, in some cases, are fully amenable to present high-throughput screening tech- nologies, such as robotic printing and fluorescence scanning devices. In the past year, several systems were described that present both natural and synthetically derived carbohydrate structures in array formats. [3] These systems differ in the mode of immobilization (covalent versus noncovalent), the surface upon which the immobilization was performed, and the [*] Prof. Dr. P. H. Seeberger, ++ E. W. Adams, + D. M. Ratner Department of Chemistry Massachusetts Institute of Technology Cambridge, MA 02139 (USA) Fax: (+ 1)617-253-2979 E-mail: seeberg@mit.edu Prof. Dr. D. R. Walt, Dr. J. Ueberfeld + The Max Tishler Laboratory for Organic Chemistry Department of Chemistry Tufts University Medford, MA 02155 (USA) E-mail: david.walt@tufts.edu Dr. B. R. O'Keefe Molecular Targets Development Program NCI Center for Cancer Research National Cancer Institute, NCI-Frederick Frederick, MD 21702 (USA) [ + ] These authors contributed equally to this work. [ ++ ] Current address: Laboratory for Organic Chemistry. ETH Höngger- berg HCI F 315, Wolfgang Pauli Strasse 10,CH 8093 Zurich. [**] This research was supported by a NDSEG Fellowship (for E.W.A.) and a NIH Biotechnology Training Grant (for D.M.R.). P.H.S. thanks GlaxoSmithKline (Scholar Award), the Alfred P. Sloan Foundation (Fellowship) and Merck for financial support. The Tufts effort was supported by a grant from NIH-NIDCR U01 DE14950-01. Angewandte Chemie 5317 Angew. Chem. Int. Ed. 2003, 42, 5317 –5320 DOI: 10.1002/anie.200351286 # 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim